Gestational diabetes mellitus in Africa: a systematic review.

BACKGROUND: Gestational diabetes mellitus (GDM) is any degree of impaired glucose tolerance first recognised during pregnancy. Most women with GDM revert to normal glucose metabolism after delivery of their babies; however, they are at risk of developing type 2 diabetes later in life as are their offspring. Determining a country's GDM prevalence can assist with policy guidelines regarding GDM screening and management, and can highlight areas requiring research. This systematic review assesses GDM prevalence in Africa. METHODS AND FINDINGS: Three electronic databases were searched without language restrictions; PubMed, Scopus and the Cochrane Library. Thirty-one search terms were searched. Eligible articles defined GDM, stated what GDM screening approaches were employed and reported GDM prevalence. The reporting quality and risk of bias within each study was assessed. The PRISMA guidelines for systematic reviews were followed. The literature search identified 466 unique records. Sixty full text articles were reviewed of which 14 were included in the systematic review. One abstract, for which the full text article could not be obtained, was also included. Information regarding GDM classification, screening methods and prevalence was obtained for six African countries; Ethiopia (n = 1), Morocco (n = 1), Mozambique (n = 1), Nigeria (n = 6), South Africa (n= 4) and Tanzania (n = 1). Prevalence figures ranged from 0% (Tanzania) to 13.9% (Nigeria) with some studies focussing on women with GDM risk factors. Most studies utilised the two hour 75 g oral glucose tolerance test and applied the World Health Organization's diagnostic criteria. CONCLUSIONS: Six countries, equating to 11% of the African continent, were represented in this systematic review. This indicates how little is known about GDM in Africa and highlights the need for further research. Considering the increasing public health burden of obesity and type 2 diabetes, it is essential that the extent of GDM is understood in Africa to allow for effective intervention programmes.This is the final published version of the article. It was originally published here: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0097871

The potential impact of the fetal genotype on maternal blood pressure during pregnancy.

The heritability of pregnancy-induced hypertension (encompassing both gestational hypertension and preeclampsia) is around 0.47, suggesting that there is a genetic component to its development. However, the maternal genetic risk variants discovered so far only account for a small proportion of the heritability. Other genetic variants that may affect maternal blood pressure in pregnancy arise from the fetal genome, for example wild-type pregnant mice carrying offspring with Cdkn1c or Stox1 disrupted develop hypertension and proteinuria. In humans, there is a higher risk for preeclampsia in women carrying fetuses with Beckwith-Wiedemann syndrome (including those fetuses with CDKN1C mutations) and a lower risk for women carrying babies with trisomy 21. Other risk may be associated with imprinted fetal growth genes and genes that are highly expressed in the placenta such as GCM1. This article reviews the current state of knowledge linking the fetal genotype with maternal blood pressure in pregnancy.MRCThis is the Author Accepted Manuscript of Petry CJ, Beardsall K, Dunger DB. "The potential impact of the fetal genotype on maternal blood pressure during pregnancy". published in the Journal of Hypertension. The published version is available at http://dx.doi.org/10.1097/HJH.000000000000021

Simple and effective exercise design for assessing in vivo mitochondrial function in clinical applications using (31)P magnetic resonance spectroscopy.

The growing recognition of diseases associated with dysfunction of mitochondria poses an urgent need for simple measures of mitochondrial function. Assessment of the kinetics of replenishment of the phosphocreatine pool after exercise using (31)P magnetic resonance spectroscopy can provide an in vivo measure of mitochondrial function; however, the wider application of this technique appears limited by complex or expensive MR-compatible exercise equipment and protocols not easily tolerated by frail participants or those with reduced mental capacity. Here we describe a novel in-scanner exercise method which is patient-focused, inexpensive, remarkably simple and highly portable. The device exploits an MR-compatible high-density material (BaSO4) to form a weight which is attached directly to the ankle, and a one-minute dynamic knee extension protocol produced highly reproducible measurements of post-exercise PCr recovery kinetics in both healthy subjects and patients. As sophisticated exercise equipment is unnecessary for this measurement, our extremely simple design provides an effective and easy-to-implement apparatus that is readily translatable across sites. Its design, being tailored to the needs of the patient, makes it particularly well suited to clinical applications, and we argue the potential of this method for investigating in vivo mitochondrial function in new cohorts of growing clinical interest.We are grateful to all the participants. This work was funded by the Clinical Research Infrastructure Grant. We thank the National Institute for Health Research (NIHR) Cambridge BioResource and S. Nutland, for facilitating the recruitment of the 24 BioResource volunteers. We thank the NIHR Cambridge Biomedical Research Centre for funding the BioResource and we also acknowledge research grants from Addenbrooke's Charitable Trust and the British Society for Pediatric Endocrinology and Diabetes. D.B.S. is supported by the Wellcome Trust [091551] and the U.K. National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. A.S. and the Siemens MAGNETOM 3T Verio scanner are funded by the NIHR via an award to the Cambridge NIHR/Wellcome Trust Clinical Research Facility. A.T. and D.B.D. are supported by the U.K. NIHR Cambridge Biomedical Research Centre. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/srep19057

Abdominal fat depots associated with insulin resistance and metabolic syndrome risk factors in black African young adults

Abstract Background Individuals of black African ethnicity tend to have less visceral adipose tissue (VAT) but more subcutaneous-abdominal adipose tissue (SCAT) than white Caucasians. However, it is unclear whether such distribution of abdominal fat is beneficial for metabolic disease risk in black individuals. Here we compared the associations between these specific abdominal fat depots, insulin sensitivity and metabolic syndrome risk. Methods A cross-sectional analysis of 76 black South African young adults (36 men; 40 women) aged 18–19 years participating in the Birth to Twenty Cohort Study had VAT and SCAT measured by MRI. The metabolic syndrome traits (blood pressure, lipid profile, fasting glucose and insulin) were measured and the values were combined into a metabolic syndrome risk score. Fasting glucose and insulin were used to derive the HOMA-index of insulin resistance (HOMA-IR). Results Compared to men, women had greater VAT (mean: 16.6 vs. 12.5 cm2) and SCAT (median 164.0 vs. 59.9 cm2). In men, SCAT (r = 0.50) was more strongly correlated to the metabolic syndrome score (MetS) than was VAT (r = 0.23), and was associated with both MetS (P = 0.001) and HOMA-IR (P = 0.001) after adjustment for VAT and total fat mass. In women, both abdominal fat compartments showed comparable positive correlations with MetS (r = 0.26 to 0.31), although these trends were weaker than in men. Conclusions In young black South African adults, SCAT appears to be more relevant than VAT to metabolic syndrome traits

The association between age at menarche and later risk of gestational diabetes is mediated by insulin resistance.

AIMS: Associations have been reported between age at menarche and the later risk of gestational diabetes. However, it is not known whether these associations reflect differences in insulin sensitivity and/or pancreatic β-cell function in pregnancy. METHODS: We examined this question in women enrolled in the prospective Cambridge Baby Growth Study who recalled their age at menarche in questionnaires during pregnancy. Polynomial logistic and linear regression models were used to relate menarche timing to the risk of gestational diabetes, both unadjusted and adjusted for the Homeostasis Model Assessments of insulin resistance (HOMA IR) and pancreatic β-cell function (HOMA B) at week 28 of pregnancy. RESULTS: Age at menarche showed a U-shaped association with gestational diabetes risk (linear term: p = 9.5 × 10-4; quadratic term: p = 1.0 × 10-3; n = 889; overall model p = 8.1 × 10-3). Age at menarche showed a negative linear association with insulin resistance (HOMA IR: β = -0.13, p = 5.2 × 10-4, n = 771), which explained the relationship between age at menarche and gestational diabetes risk (adjusted linear term going from p = 0.03-0.08; adjusted quadratic term going from p = 0.04-0.08; n = 771). Age at menarche also showed a negative linear association with β-cell function (HOMA B: β = -0.11, p = 2.8 × 10-3, n = 771) but this did not attenuate the relationship between age at menarche and gestational diabetes (adjusted linear term p = 0.02; adjusted quadratic term p = 0.03, n = 771). CONCLUSIONS: These results suggest that the associations between age at menarche and risk of gestational diabetes and raised pregnancy glucose concentrations may be mediated by insulin resistance.Funding for this study has come from the Wellbeing of Women (the Royal College of Obstetricians and Gynaecologists, UK) (RG1644). Other core funding has come from the Medical Research Council (7500001180, G1001995, U106179472), European Union Framework 5 (QLK4-1999-01422), the Mothercare Charitable Foundation (RG54608), Newlife Foundation for Disabled Children (07/20), and the World Cancer Research Fund International (2004/03). In addition, there has been support from National Institute for Health Research Cambridge Biomedical Research Centre. KO is supported by the Medical Research Council (Unit Programme number: MC_UU_12015/2)

Pharmacokinetics of diluted (U20) insulin aspart compared with standard (U100) in children aged 3-6 years with type 1 diabetes during closed-loop insulin delivery: a randomised clinical trial.

AIMS/HYPOTHESIS: The aim of this study was to compare the pharmacokinetics of two different concentrations of insulin aspart (B28Asp human insulin) in children aged 3-6 years with type 1 diabetes. METHODS: Young children with type 1 diabetes underwent an open-label, randomised, two-period crossover study in a clinical research facility, 2-6 weeks apart. In random order, diluted (1:5 dilution with saline [154 mmol/l NaCl]; 20 U/ml) or standard strength (100 U/ml) insulin aspart was administered via an insulin pump as a meal bolus and then overnight by closed-loop insulin delivery as determined by a model predictive algorithm. Plasma insulin was measured every 30-60 min from 17:00 hours on day 1 to 8:00 hours on day 2. We measured the time-to-peak insulin concentration (tmax), insulin metabolic clearance rate (MCR(I)) and background insulin concentration (ins(c)) using compartmental modelling. RESULTS: Eleven children (six male; age range 3.75-6.96 years, HbA1c 7.6% ± 1.3% [60 ± 14 mmol/mol], BMI standard deviation score 1.0 ± 0.8, duration of diabetes 2.2 ± 1.0 years, total daily dose 12.9 [10.6-16.5] U, fasting C-peptide concentration 5 [5-17.1] pmol/l; mean ± SD or median [interquartile range]) participated in the study. No differences between standard and diluted insulin were observed in terms of t max (59.2 ± 14.4 vs 61.6 ± 8.7) min for standard vs diluted, p = 0.59; MCR I (1.98 × 10(-2) ± 0.99 × 10(-2) vs 1.89 × 10(-2) ± 0.82 × 10(-2) 1/kg/min, p = 0.47), and ins c (34 [1-72] vs 23 [3-65] pmol/l, p = 0.66). However, t max showed less intersubject variability following administration of diluted aspart (SD 14.4 vs 8.7 min, p = 0.047). CONCLUSIONS/INTERPRETATION: Diluting insulin aspart does not change its pharmacokinetics. However, it may result in less variable absorption and could be used in young children with type 1 diabetes undergoing closed-loop insulin delivery. TRIAL REGISTRATION: Clinicaltrials.gov NCT01557634. FUNDING: FUNDING was provided by the JDRF, 7th Framework Programme of the European Union, Wellcome Trust Strategic Award and the National Institute for Health Research Cambridge Biomedical Research Centre.Funding was provided by the JDRF (grant number 22-2011- 668), 7th Framework Programme of the European Union (Spidiman project; grant agreement number 305343), Wellcome Trust Strategic Award (100574/Z/12/Z) and the National Institute for Health Research Cambridge Biomedical Research Centre.This is the final published version. It first appeared at http://link.springer.com/article/10.1007%2Fs00125-014-3483-6

Sensor Life and Overnight Closed Loop: A Randomized Clinical Trial.

BACKGROUND: Closed-loop (CL) systems direct insulin delivery based on continuous glucose monitor (CGM) sensor values. CGM accuracy varies with sensor life, being least accurate on day 1 of sensor insertion. We evaluated the effect of sensor life (enhanced Enlite, Medtronic MiniMed, Northridge, CA) on overnight CL. METHODS: In an open-label, randomized, 2-period, inpatient crossover pilot study, 12 adolescents on insulin pump (age 16.7 ± 1.9 years; HbA1c 66 ± 10 mmol/mol) attended a clinical research facility on 2 overnight occasions. In random order, participants received CL on day 1 or on day 3-4 after sensor insertion. During both periods, glucose was automatically controlled by a model predictive control algorithm informed by sensor glucose. Plasma glucose was measured every 30 to 60 min. RESULTS: During overnight CL (22:30 to 07:30), the proportion of time with plasma glucose readings in the target range (3.9-8.0 mmol/l, primary endpoint) when initiated on day 1 of sensor insertion vs day 3-4 were comparable (58 ± 32% day 1 vs 56 ± 36% day 3-4; P = .34), and there were no significant differences between interventions in terms of mean plasma glucose ( P = .26), percentage time above 8.0 mmol/l ( P = .49), and time spent below 3.9 mmol/l ( P = .93). Sensor accuracy varied with sensor life (mean absolute relative difference 19.8 ± 15.0% on day 1 and 13.7 ± 10.2% on day 3 to 4). Sensor glucose tended to under-read plasma glucose inflating benefits of CL on glucose control. CONCLUSIONS: In spite of differences in sensor accuracy, overnight CL glucose control informed by sensor glucose on day 1 or day 3-4 after sensor insertion was comparable. The model predictive controller appears to mitigate against sensor inaccuracies.This work was funded by the JDRF (#22-2011-668). Additional support for the Artificial Pancreas work by National Institute for Health Research Cambridge Biomedical Research Centre and Wellcome Strategic Award (100574/Z/12/Z). Medtronic supplied study pump, translator device, sensor transmitter, Amber user interface, and supported regulatory approval

Feasibility of overnight closed-loop therapy in young children with type 1 diabetes aged 3-6 years: comparison between diluted and standard insulin strength.

OBJECTIVE: To assess feasibility of overnight closed-loop therapy in young children with type 1 diabetes and contrast closed loop using diluted versus standard insulin strength. RESEARCH DESIGN AND METHODS: Eleven children (male 6; age range 3.75-6.96 years; glycated hemoglobin 60 (14) mmol/mol; body mass index SD score 1.0 (0.8); diabetes duration 2.2 (1.0) years, mean (SD); total daily dose 12.9 (10.6, 16.5) IU/day, median (IQR)) were studied at a clinical research facility on two occasions. In random order, participants received closed loop with diluted insulin aspart (CL_Dil; 20 IU/mL) or closed loop with standard aspart (CL_Std; 100 IU/mL) from 17:00 until 8:00 the following morning. Children consumed an evening meal at 17:00 (44 (12) gCHO) and an optional bedtime snack (6 (7) gCHO) identical on both occasions. Meal insulin boluses were calculated by standard pump bolus calculators. Basal rates on insulin pump were adjusted every 15 min as directed by a model-predictive-control algorithm informed by a real-time glucose sensor values. RESULTS: Mean plasma glucose was 122 (24) mg/dL during CL_Dil vs 122 (23) mg/dL during CL_Std (p=0.993). The time spent in the target glucose range 70-145 mg/dL was 83 (70, 100)% vs 72 (54, 81)% (p=0.328). Time above 145 mg/dL was 13 (0, 27)% vs 19 (10, 45)% (p=0.477) and time spent below 70 mg/dL was 0.0 (0.0, 1.4)% vs 1.4 (0.0, 11.6)% (p=0.161). One asymptomatic hypoglycemia below 63 mg/dL occurred in one participant during CL_Dil versus six episodes in five participants during CL_Std (p=0.09). Glucose variability measured by CV of plasma glucose tended to be reduced during CL_Dil (20% (13, 31) vs 32% (24, 42), p=0.075). CONCLUSIONS: In this feasibility study, closed-loop therapy maintained good overnight glucose control with tendency towards reduced hypoglycemia and reduced glucose variability using diluted insulin. TRIAL REGISTRATION NUMBER: clinicaltrials.gov Identifier: NCT01557634.This work was funded by the Juvenile Diabetes Research Foundation (JDRF Grant Number: 22-2011-668) and supported by NIHR Cambridge Biomedical Research Centre.This is the final published version. It first appeared at http://drc.bmj.com/content/2/1/e000040.abstract

Nutritional status and HIV in rural South African children.

BACKGROUND: Achieving the Millennium Development Goals that aim to reduce malnutrition and child mortality depends in part on the ability of governments/policymakers to address nutritional status of children in general and those infected or affected by HIV/AIDS in particular. This study describes HIV prevalence in children, patterns of malnutrition by HIV status and determinants of nutritional status. METHODS: The study involved 671 children aged 12-59 months living in the Agincourt sub-district, rural South Africa in 2007. Anthropometric measurements were taken and HIV testing with disclosure was done using two rapid tests. Z-scores were generated using WHO 2006 standards as indicators of nutritional status. Linear and logistic regression analyses were conducted to establish the determinants of child nutritional status. RESULTS: Prevalence of malnutrition, particularly stunting (18%), was high in the overall sample of children. HIV prevalence in this age group was 4.4% (95% CI: 2.79 to 5.97). HIV positive children had significantly poorer nutritional outcomes than their HIV negative counterparts. Besides HIV status, other significant determinants of nutritional outcomes included age of the child, birth weight, maternal age, age of household head, and area of residence. CONCLUSIONS: This study documents poor nutritional status among children aged 12-59 months in rural South Africa. HIV is an independent modifiable risk factor for poor nutritional outcomes and makes a significant contribution to nutritional outcomes at the individual level. Early paediatric HIV testing of exposed or at risk children, followed by appropriate health care for infected children, may improve their nutritional status and survival.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are